Neutron fibre diffraction studies of amyloid using H2O/D2O isotopic replacement

Abstract

The first neutron fibre diffraction studies of an amyloid system are presented. The techniques used to prepare the large samples needed are described, as well as the procedures used to isotopically replace H2O in the sample by D2O. The results demonstrate the feasibility of this type of approach for the pursuit of novel structural analyses that will strongly complement X-ray fibre diffraction studies and probe aspects of amyloid structure that to date have remained obscure. The approach is demonstrated using an amyloid form of the peptide NSGAITIG, but is equally applicable for the study of other systems such as Alzheimer's Aβ peptide.

Figure 1

Fibre array constructed for neutron diffraction experiments on the peptide NSGAITIG. The sample consists of approximately 150 individual fibres each having a diameter of 50 µm.

Figure 2

Neutron fibre diffraction data recorded from amyloid fibres of NSGAITIG in both H₂O and D₂O environments, shown alongside corresponding X-ray patterns. Low-angle data are shown in (a)–(c) and high-angle data in (d)–(f). (a, d) Neutron data from amyloid sample in H₂O solvent. (b, e) Neutron data from amyloid sample in D₂O solvent (c, f) X-ray data from amyloid sample in H₂O solvent.